Serotonin Syndrome Gabriel Tsao, MS3 Ben Berk, MS4

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Serotonin SyndromeGabriel Tsao, MS3Ben Berk, MS4
Left Brain vs Right Brain

• Gabriel Tsao, MS3
• Stanford University
• School of Medicine

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Case

• ID/CC 45 yo w/ h/o bipolar disorder s/p sigmoid
  colectomy for adeno CA.
• Prior outpatient meds Lexapro 10, Seroquel 800
  qhs, Keppra 500/1000, Xanax gt4mg qd, Ambien 10
  qhs
• Hospital course acutely psychotic post-op
• Max Inpatient Meds Lexapro 10, Seroquel 800 qhs,
  Keppra 500 q8, Valproic Acid 750/1000, Versed gtt
  6, clonidine patch, Ativan 3/3/3/5, Fentanyl gtt
  200, Haldol 4/4/4/10, donepazil 10, zofran 8, and
  olanzapine 5mg q8h PRN

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Physical exam

• Hyperthermia 40º, tremor, agitation, diarrhea,
  diaphoretic, HTN
• Psych recommended discontinuing all psychiatric
  medications, only on valium and fentanyl.
• Within 48 hrs, pt dramatically recovered

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Serotonin Syndrome

• Libby Zion (1984)
• An 18 yo college student who presented to the
  hospital with a fever of 103.5, agitation,
  confusion, jerking motions.
• Had been taking an antidepressent, phenelzine.
• Given meperidine in the hospital
• Increasingly agitated, restrained
• Six hours later, temp 107, cardiac arrest

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Public Outrage

• Ms. Zion was seen only be an intern and R2
• The R2 had 40 other patients to cover
• 36 hour shift
• Father was a writer for NY Times
• Story featured in NY Times, Newsweek, Washington
  Post, 60 Minutes
• 1986 DA convened Grand Jury
• 1989 NY State adopted 80 hr resident work week
  restriction w/ supervision guidelines
• 2003 ACGME adopts similar standards

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Incidence of Serotonin Syndrome

• Observed in all age groups
• Increasing incidence thought to be associated
  with increased use of serotonergic agents
• 2004 Toxic Exposure Surveillance System
• 48,204 exposures to SSRIs that resulted in
  moderate or major outcomes in 8187 pts and 103
  deaths.
• Occurs in 14-16 of persons who overdose SSRIs
• Incidence difficult to assess
• 85 of physicians in 1999 were unaware of
  serotonin syndrome as a clinical diagnosis

Mackay FJ, et al. Antidepressants and the
serotonin syndrome in general practice. Br J Gen
Pract 1999 49871-9.
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Serotonin

• In the CNS
• Modulates attention, behavior and
  thermoregulation
• In the Periphery
• Vascular tone and gastric motility

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Serotonin Syndrome

• Stimulation of postsynaptic 5HT1A and 5HT1B
  receptors implicated
• No one receptor solely responsible
• Any combination of drugs that has net effect
  increased serotonin neurotransmission
• Classically two simultaneously, but can be with
  initiation of a single drug or increasing dose in
  a sensitive individual
• Seen in intentional overdoses

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Features of Serotonin Syndrome

• Classic clinical triad
• Mental status changes
• Autonomic hyperactivity
• Neuromuscular abnormalities
• Wide ranging symptoms

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Diagnosis

• Hunter Criteria (84 sensitive, 97 specific)
• Must have taken a serotonergic agent
• Plus one of following
• Spontaneous clonus
• Inducible clonus plus agitation or diaphoresis
• Ocular clonus plus agitation or diaphoresis
• Tremor and hyper-reflexia
• Hypertonia
• Temperature above 38 plus ocular or inducible
  clonus

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Serotonin Syndrome vs NMS

• Development
• SS develops over 24 hrs, often 6 hrs
• NMS develops over days to weeks
• Neuromuscular responses
• SS characterized by hyperreactivity
• Tremor, hyperreflexia, myoclonus
• NMS involves sluggish responses
• Rigidity, bradyreflexia
• Resolution
• SS usually resolves within 24 hrs
• NMS requires an average of 9 days

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Associated Drugs

• MR meds

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Management

• Removal of precipitating drugs
• Most cases typically resolve within 24 hrs of
  removal
• Administration of 5HT antagonists
• Cyproheptadine 12 mg initial dose, 2 mg q1h
• Control of agitation
• Benzodiazepines regardless of symptom severity
• Physical restraints alone ill-advised (lactic
  acidosis, temp)
• Control of hyperthermia (gt41.1)
• Sedation, neuromuscular paralysis, orotracheal
  intubation
• Control of autonomic instability

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Pitfalls

• Misdiagnosis of serotonin syndrome
• Failure to comprehend rapidity of progression
• Failure to comprehend adverse pharm effects
• Muscle rigidity can mask clonus and hyperreflexia
• If serotonin syndrome not obvious
• Withhold 5HT antagonist therapy
• Provide all other therapy
• Anticipate need for aggressive therapy

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Thanks

• Dr. Purtill
• Dr. Spain
• Dr. Patterson
• Team
• Dr. Garland, Amy, Sarah, Geoff and Geoff, Ron,
  Rich, Rebecca, Ngoc, Ben
• Our twins in the ICU